FDA

Leqvio now approved as monotherapy for hypercholesterolemia

August 6, 2025

FDA approved a label update for Leqvio (inclisiran), a small interfering RNA directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA, enabling its use as monotherapy along with diet and exercise to reduce LDL-C in adults with hypercholesterolemia.

The updated label removes the requirement for Leqvio to be used as an adjunct to statin therapy. Other updates include revising "primary hyperlipidemia" to the more specific term of "hypercholesterolemia" throughout the label, to more accurately focus on LDL-C reduction.

Efficacy

Approval was based on data from the V-Mono trial (NCT05763875) that included 350 participants with fasting LDL-C of 100mg/dL to 190mg/dL and 10-year predicted ASCVD risk <7.5%. Participants were randomized (2:1:1) to inclisiran, ezetimibe, or placebo. Primary endpoint was percentage change in LDL-C from baseline.

The mean percentage change in LDL-C from baseline at day 150 for placebo was 1.4%, for ezetimibe −11.2%, and inclisiran −46.5%. The difference in the change from baseline with inclisiran vs. placebo was −47.9% and vs. ezetimibe was −35.4% (both P < 0.0001).

Safety

No new safety signals were reported in the V-Mono trial. The most common adverse reactions in clinical trials (≥ 3%) were injection site reaction, arthralgia, and bronchitis.

Sources:

Leqvio (incliseran) [package insert]. Food and Drugs Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/214012s016lbl.pdf Revised July 2025. Accessed August 5, 2025.

Novartis twice-yearly Leqvio® (inclisiran) receives FDA approval for new indication enabling first-line use. [News release]. 2025. https://www.empr.com/news/leqvio-monotherapy-approved-for-adults-with-hypercholesterolemia/

Taub PR, et al. (2025, May 5). J Am Coll Cardiol. Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40392667/